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首页> 外文期刊>Neurobiology of disease >The loss of interneuron functional diversity in the piriform cortex after induction of experimental epilepsy
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The loss of interneuron functional diversity in the piriform cortex after induction of experimental epilepsy

机译：诱发实验性癫痫后梨状皮层中神经元功能多样性的丧失

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Interneuronal functional diversity is thought to be an important factor in the control of neural network oscillations in many brain regions. Specifically, interneuron action potential firing patterns are thought to modulate brain rhythms. In neurological disorders such as epilepsy where brain rhythms are significantly disturbed interneuron function is largely unexplored. Thus the purpose of this study was to examine the functional diversity of piriform cortex interneurons (PC; an area of the brain that easily supports seizures) before and after kindling-induced epilepsy. Using cluster analysis, we found five control firing behaviors. These groups were termed: non-adapting very high frequency (NAvHF), adapting high frequency (AHF), adapting low frequency (ALF), strongly adapting low frequency (sALF), and weakly adapting low frequency (wALF). A morphological analysis showed these spiking patterns were not associated with any specific interneuronal morphology although we found that most of the cells displaying NAvHF firing pattern were multipolar. After kindling about 40% of interneuronal firing pattern changed, and neither the NAvHF nor the wALF phenotypes were found. We also found that in multipolar interneurons a long-lasting potassium current was increased. A qPCR analysis indicated Kv1.6 subtype was up-regulated after kindling. An immunocytochemical analysis showed that Kv1.6 protein expression on parvalbumin (multipolar) interneurons increased by greater than 400%. We also examined whether these changes could be due to the selective death of a subset of interneurons but found that there was no change in cell number. These data show an important loss of the functional diversity of interneurons in the PC. Our data suggest that under pathophysiological condition interneurons are plastic resulting in the attenuation of high frequency network oscillations in favor of low frequency network activity. This may be an important new mechanism by which network synchrony is disturbed in epileptic seizures.
机译：神经元间功能多样性被认为是控制许多大脑区域神经网络振荡的重要因素。具体而言，人们认为神经元内动作电位激发模式可调节脑节律。在诸如癫痫病的神经系统疾病中，脑节律被显着干扰，神经元的功能在很大程度上尚待研究。因此，本研究的目的是检查点燃诱发的癫痫发作前后的梨状皮层中间神经元（PC;易于支持癫痫发作的大脑区域）的功能多样性。使用聚类分析，我们发现了五个控制触发行为。这些组被称为：不适应甚高频（NAvHF），适应高频（AHF），适应低频（ALF），强烈适应低频（sALF）和弱适应低频（wALF）。形态分析表明，这些尖峰模式与任何特定的神经元间形态均不相关，尽管我们发现显示NAvHF放电模式的大多数细胞是多极的。点燃后，约40％的神经元放电模式改变，并且没有发现NAvHF和wALF表型。我们还发现，在多极中间神经元中，持久的钾电流增加了。 qPCR分析表明，点燃后Kv1.6亚型上调。免疫细胞化学分析显示，小白蛋白（多极）中间神经元上的Kv1.6蛋白表达增加了400％以上。我们还检查了这些变化是否可能是由于中间神经元子集的选择性死亡所致，但发现细胞数量没有变化。这些数据表明PC中中间神经元功能多样性的重大损失。我们的数据表明，在病理生理情况下，中间神经元是可塑性的，导致高频网络振荡的衰减，有利于低频网络活动。这可能是重要的新机制，在癫痫性发作中网络同步受到干扰。

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